The genetic basis of complex traits: from yeast to humans

Project Summary The evolutionary origins of complex polygenic traits remain an enduring enigma. Although introductory genetics is often taught with simple monogenic examples such as Mendel’s peas, most traits—including all common human diseases—actually result from multitudes of interacting loci. Genome-wide association studies (GWAS) have done a great deal to illustrate this, as well as the fact that variation in gene expression cis- regulation—such as promoters and enhancers—accounts for most phenotypic variation. However, uncovering the evolutionary origins of complex traits is still a major challenge. My lab has developed experimental and computational methods to pinpoint the genes contributing to complex traits, with a focus on evolutionary adaptations involving gene expression regulation. Our main focus is on two methods: high-throughput precision genome editing and allele-specific gene expression analysis in hybrids. These methods have enabled us to implicate and experimentally validate causal genes and genetic variants underlying complex traits in archaea, yeast, flies, fish, mice, and humans. Moreover, the code and genetic constructs underlying our methods are freely available to the scientific community.